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- Definition.
- Pain management.
- Clinical toxicology testing types.
- References ranges
( Lab.I ) 10th Oct. 2019
A. L. Ghazwan Ahmed Brifkani
M.Sc. In Toxicology
Clinical toxicology: Can be defined as the
analysis of drugs and toxins in body fluids for the
purpose of patient care. The mission of the clinical
toxicology laboratory is to effectively utilize available
laboratory resources and expertise to provide
clinically useful toxicology tests to support the
needs of the patients.
 The two traditional clinical toxicology services are therapeutic drug
monitoring (TDM) and emergency toxicology. These involves testing for
drugs in a patient who comes to the emergency department in a hospital
with signs and symptoms related to drug toxicity. In this case,
laboratories may perform a "drugs of abuse screen" by a technology
known as immunoassay on blood or urine obtained from a patient. The
most commonly abused drugs, such as amphetamines, barbiturates,
benzodiazepines, cocaine, marijuana, methadone, and opioids, are
screened first, and therapeutic drugs, such as valproic acid , salicylate,
carbamazepine, and cyclosporine.

 In patients who are taken to the emergency
department for a drug overdose or toxicity,
confirmation testing can be performed using
more sophisticated instrumentation such as
chromatography (gas, liquid, or thin layer) alone
or in combination with mass spectrometry if it is
needed.
 Management of the patient can be summarized in two
meaning:
 1- (what to test for)!!!?, by the availability of suitable
analytical methods and technical resources
 2- (how to test for) !!!?.
Clinical Toxicology
KEY CONCEPTS
Poisoning can result from exposure to excessive doses of any chemical, with
medicines being responsible for most childhood and adult poisonings.
Immediate first aid may reduce the development of serious poisoning, and
consultation with a poison control center may indicate the need for further therapy.
The use of ipecac syrup, gastric lavage, whole bowel irrigation, and cathartics has
fallen out of favor as routine therapies, whereas activated charcoal remains useful for
gastric decontamination of appropriate patients.
Antidotes can prevent or reduce the toxicity of certain poisons, but symptomatic and
supportive care is essential for all patients.
Acute acetaminophen poisoning produces severe liver injury and occasionally kidney
failure.
A determination of serum acetaminophen concentration may indicate
whether there is risk of hepatotoxicity and the need for acetylcysteine
therapy.
Anticholinesterase insecticides may produce life-threatening respiratory
distress and paralysis by all routes of exposure and can be treated with
symptomatic care, atropine, and pralidoxime. (benzodiazepines).
An overdose of calcium channel antagonists will produce severe
hypotension and bradycardia, which can be treated with supportive
care, calcium, insulin with supplemental dextrose, and glucagon.
Poisoning with iron-containing drugs produces vomiting, gross
gastrointestinal bleeding, shock,
metabolic acidosis, and coma and can be treated with supportive care and
deferoxamine.
Acute opioid poisoning and overdose can produce life threatening
respiratory depression that can be treated with assisted ventilation and
naloxone.
Overdoses of tricyclic antidepressants can cause arrhythmias, such as
prolonged QRS intervals.
and ventricular dysrhythmias, coma, respiratory depression, and seizures,
are treated with symptomatic care and IV sodium bicarbonate.
By automated analytical methods.
1- Immunoassay & hormonal tests (Elecsys, Chorus)
2- Biochemical assay (Cobas, Vidase)
3- Identification of microorganism & antibiotic
sensitivities test (ID, AST) by phoenix &Vitek
instruments.
-
- Identification of microorganisms (Infectious disease diagnosis)
- AST
 Amphetamines
 Barbiturates
 Benzodiazepines
 Cannabinoids
 Cocain Metabolite
 Ethanol
 Methadone
 Opiates
 Phencyclidine
 Propoxyphene
Drug of abuse in
urine
Positive cut-
off levels
Min & max. detection time in
urine
Good reactivity
Cocaine Metabolite 300 ug/L
2 d to 4 d (occasional use) &
22 d (depends on frequency &
intensity of use)
Benzoylecgonine
Opiates
300 ug/L 0.5 d to 3 d (small dose) & 11
d (large dose)
Morphine,
Codeine, Heroin
Cannabinoids 50 ug/L
1 d to 7 d (occasional use)-95
d (chronic use)
Cannabis
Amphetamines
(stimulant amines)
1000 ug/L 1 d to 3 d (small dose) & 6 to
9 d (large dose)
d-Amphetamine d-
Methamphetamine
(Crystal Meth)
Barbiturates 300 ug/L
1 h to 4 d (Shorting-acting) 7 d
to weeks (long acting)
Phenobarbital
Glutethimide
Benzodiazepine 300 ug/L
3 d to weeks (Have variable
pharmacokinetic variables)
Diazepam
Flurazepam
Clonazepam
Alcohol 10 mg/dL
0.01 gm/dl
GLC identification of volatiles
Ethanol, Acetone
Following are some of the drugs that are commonly checked, followed by the
normal target levels:
•Acetaminophen: varies with use
•Amikacin: 15 to 25 mcg/mL
•Carbamazepine: 5 to 12 mcg/mL
•Chloramphenicol: 10 to 20 mcg/mL , if <<< Aplastic anemia
•Digoxin: 0.8 to 2.0 ng/mL
•Gentamicin: 5 to 10 mcg/mL
•Lithium: 0.8 to 1.2 mEq/L
•Phenobarbital: 10 to 30 mcg/mL
•Phenytoin: 10 to 20 mcg/mL
•Salicylate: 100 to 250 mcg/mL
•Tobramycin: 5 to 10 mcg/mL <<< if Ototoxicity .
•Valproic acid: 50 to 100 mcg/mL
Note:
mcg/mL = microgram per milliliter
ng/mL = nanogram per milliliter
mEq/L = milliequivalents per liter
mcmol = micromole
Following are toxic levels for some of the
therapeutic drugs that are commonly checked:
•Acetaminophen: greater than 250 mcg/mL
•Amikacin: greater than 25 mcg/mL
•Carbamazepine: greater than 12 mcg/mL
•Chloramphenicol: greater than 25 mcg/mL
•Digoxin: greater than 2.4 ng/mL
•Gentamicin: greater than 12 mcg/mL
•Lithium: greater than 2.0 mEq/L
•Phenobarbital: greater than 40 mcg/mL
•Phenytoin: greater than 30 mcg/mL
•Salicylate: greater than 300 mcg/mL
•Valproic acid: greater than 100 mcg/mL
 Albumin
 Ammonia
 Bicarbonate
 Bilirubin-direct
 Bilirubin-total
 Calcium
 Cholesterol
 HDL-Cholesterol
 LDL-Cholesterol
 VLDL
 Creatinine.
 Fructosamine
 Glucose
 Iron
 Lactate
 Magnesium
 Phosphorus
 Total Protein
 Total Protein U / CSF
 Triglycerides
 Urea
 Uric Acid
 Albumin (immuno.) IgG
 ASLO (Antistreptolysin O titre)
 CRP Prealbumin
 CRP High Sensitivity RF
 Microglobulin HbA1c (whole blood)
 Beta-2 microglobulin
 ALP (Alkaline phosphatase )
 ALT/GPT
 AST / GOT
 Amylase–total serum <<< Evaluation of pancreatic function
 Amylase-pancr. Serum <<< diagnosis and management of
pancreatitis
 Cholinesterase
 CK
 Lipase
 Sodium
 Chloride
 Potassium
 25-(OH)2 Vitamin D3
 Intact PTH
 N-MID Osteocalcin
 Ferritin
 Vitamin B12
 Folate
 RBC Folate
 Anti TSH-receptor
 T3
 T4
 T-Uptake
 TSH
 ACTH (Adrenocorticotropic hormone)
 C-peptide
 Cortisol
 Estradiol
 Insulin
 Progesterone
 Prolactin
 SHBG (Sex hormone-binding globulin )
 Testosterone
 CK-MB (mass) (creatine kinase isoenzyme MB)
 CK-MB (mass) STAT
 Digoxin
 Digitoxin
 Myoglobin
 Troponin T
 Troponin T STAT
Clinical-toxicology-lab-1-2019-2020.pptx
Clinical-toxicology-lab-1-2019-2020.pptx

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Clinical-toxicology-lab-1-2019-2020.pptx

  • 1. - Definition. - Pain management. - Clinical toxicology testing types. - References ranges ( Lab.I ) 10th Oct. 2019 A. L. Ghazwan Ahmed Brifkani M.Sc. In Toxicology
  • 2. Clinical toxicology: Can be defined as the analysis of drugs and toxins in body fluids for the purpose of patient care. The mission of the clinical toxicology laboratory is to effectively utilize available laboratory resources and expertise to provide clinically useful toxicology tests to support the needs of the patients.
  • 3.  The two traditional clinical toxicology services are therapeutic drug monitoring (TDM) and emergency toxicology. These involves testing for drugs in a patient who comes to the emergency department in a hospital with signs and symptoms related to drug toxicity. In this case, laboratories may perform a "drugs of abuse screen" by a technology known as immunoassay on blood or urine obtained from a patient. The most commonly abused drugs, such as amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, methadone, and opioids, are screened first, and therapeutic drugs, such as valproic acid , salicylate, carbamazepine, and cyclosporine. 
  • 4.  In patients who are taken to the emergency department for a drug overdose or toxicity, confirmation testing can be performed using more sophisticated instrumentation such as chromatography (gas, liquid, or thin layer) alone or in combination with mass spectrometry if it is needed.
  • 5.  Management of the patient can be summarized in two meaning:  1- (what to test for)!!!?, by the availability of suitable analytical methods and technical resources  2- (how to test for) !!!?.
  • 6. Clinical Toxicology KEY CONCEPTS Poisoning can result from exposure to excessive doses of any chemical, with medicines being responsible for most childhood and adult poisonings. Immediate first aid may reduce the development of serious poisoning, and consultation with a poison control center may indicate the need for further therapy. The use of ipecac syrup, gastric lavage, whole bowel irrigation, and cathartics has fallen out of favor as routine therapies, whereas activated charcoal remains useful for gastric decontamination of appropriate patients. Antidotes can prevent or reduce the toxicity of certain poisons, but symptomatic and supportive care is essential for all patients. Acute acetaminophen poisoning produces severe liver injury and occasionally kidney failure.
  • 7. A determination of serum acetaminophen concentration may indicate whether there is risk of hepatotoxicity and the need for acetylcysteine therapy. Anticholinesterase insecticides may produce life-threatening respiratory distress and paralysis by all routes of exposure and can be treated with symptomatic care, atropine, and pralidoxime. (benzodiazepines). An overdose of calcium channel antagonists will produce severe hypotension and bradycardia, which can be treated with supportive care, calcium, insulin with supplemental dextrose, and glucagon.
  • 8. Poisoning with iron-containing drugs produces vomiting, gross gastrointestinal bleeding, shock, metabolic acidosis, and coma and can be treated with supportive care and deferoxamine. Acute opioid poisoning and overdose can produce life threatening respiratory depression that can be treated with assisted ventilation and naloxone. Overdoses of tricyclic antidepressants can cause arrhythmias, such as prolonged QRS intervals. and ventricular dysrhythmias, coma, respiratory depression, and seizures, are treated with symptomatic care and IV sodium bicarbonate.
  • 9. By automated analytical methods. 1- Immunoassay & hormonal tests (Elecsys, Chorus) 2- Biochemical assay (Cobas, Vidase) 3- Identification of microorganism & antibiotic sensitivities test (ID, AST) by phoenix &Vitek instruments.
  • 10. - - Identification of microorganisms (Infectious disease diagnosis) - AST
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  • 17.  Amphetamines  Barbiturates  Benzodiazepines  Cannabinoids  Cocain Metabolite  Ethanol  Methadone  Opiates  Phencyclidine  Propoxyphene
  • 18.
  • 19. Drug of abuse in urine Positive cut- off levels Min & max. detection time in urine Good reactivity Cocaine Metabolite 300 ug/L 2 d to 4 d (occasional use) & 22 d (depends on frequency & intensity of use) Benzoylecgonine Opiates 300 ug/L 0.5 d to 3 d (small dose) & 11 d (large dose) Morphine, Codeine, Heroin Cannabinoids 50 ug/L 1 d to 7 d (occasional use)-95 d (chronic use) Cannabis Amphetamines (stimulant amines) 1000 ug/L 1 d to 3 d (small dose) & 6 to 9 d (large dose) d-Amphetamine d- Methamphetamine (Crystal Meth) Barbiturates 300 ug/L 1 h to 4 d (Shorting-acting) 7 d to weeks (long acting) Phenobarbital Glutethimide Benzodiazepine 300 ug/L 3 d to weeks (Have variable pharmacokinetic variables) Diazepam Flurazepam Clonazepam Alcohol 10 mg/dL 0.01 gm/dl GLC identification of volatiles Ethanol, Acetone
  • 20. Following are some of the drugs that are commonly checked, followed by the normal target levels: •Acetaminophen: varies with use •Amikacin: 15 to 25 mcg/mL •Carbamazepine: 5 to 12 mcg/mL •Chloramphenicol: 10 to 20 mcg/mL , if <<< Aplastic anemia •Digoxin: 0.8 to 2.0 ng/mL •Gentamicin: 5 to 10 mcg/mL •Lithium: 0.8 to 1.2 mEq/L •Phenobarbital: 10 to 30 mcg/mL •Phenytoin: 10 to 20 mcg/mL •Salicylate: 100 to 250 mcg/mL •Tobramycin: 5 to 10 mcg/mL <<< if Ototoxicity . •Valproic acid: 50 to 100 mcg/mL Note: mcg/mL = microgram per milliliter ng/mL = nanogram per milliliter mEq/L = milliequivalents per liter mcmol = micromole
  • 21. Following are toxic levels for some of the therapeutic drugs that are commonly checked: •Acetaminophen: greater than 250 mcg/mL •Amikacin: greater than 25 mcg/mL •Carbamazepine: greater than 12 mcg/mL •Chloramphenicol: greater than 25 mcg/mL •Digoxin: greater than 2.4 ng/mL •Gentamicin: greater than 12 mcg/mL •Lithium: greater than 2.0 mEq/L •Phenobarbital: greater than 40 mcg/mL •Phenytoin: greater than 30 mcg/mL •Salicylate: greater than 300 mcg/mL •Valproic acid: greater than 100 mcg/mL
  • 22.  Albumin  Ammonia  Bicarbonate  Bilirubin-direct  Bilirubin-total  Calcium  Cholesterol  HDL-Cholesterol  LDL-Cholesterol  VLDL  Creatinine.  Fructosamine  Glucose  Iron  Lactate  Magnesium  Phosphorus  Total Protein  Total Protein U / CSF  Triglycerides  Urea  Uric Acid
  • 23.  Albumin (immuno.) IgG  ASLO (Antistreptolysin O titre)  CRP Prealbumin  CRP High Sensitivity RF  Microglobulin HbA1c (whole blood)  Beta-2 microglobulin
  • 24.  ALP (Alkaline phosphatase )  ALT/GPT  AST / GOT  Amylase–total serum <<< Evaluation of pancreatic function  Amylase-pancr. Serum <<< diagnosis and management of pancreatitis  Cholinesterase  CK  Lipase
  • 25.  Sodium  Chloride  Potassium  25-(OH)2 Vitamin D3  Intact PTH  N-MID Osteocalcin
  • 26.  Ferritin  Vitamin B12  Folate  RBC Folate
  • 27.  Anti TSH-receptor  T3  T4  T-Uptake  TSH
  • 28.  ACTH (Adrenocorticotropic hormone)  C-peptide  Cortisol  Estradiol  Insulin  Progesterone  Prolactin  SHBG (Sex hormone-binding globulin )  Testosterone
  • 29.  CK-MB (mass) (creatine kinase isoenzyme MB)  CK-MB (mass) STAT  Digoxin  Digitoxin  Myoglobin  Troponin T  Troponin T STAT

Editor's Notes

  1. Aplastic anemia, is a rare disease in which the bone marrow and the hematopoietic stem cells that reside there are damaged. This causes a deficiency of all three blood cell types (pancytopenia): red blood cells (anemia),white blood cells (leukopenia), and platelets (thrombocytopenia). Aplastic  refers to inability of the stem cells to generate mature blood cells.
  2. The fructosamine test is a tool for measuring how well your diabetes treatment program is working that is somewhere between home blood glucose monitoring and Hemoglobin A1c. VLDL stands for very-low-density lipoprotein. Your liver makes VLDL cholesterol and releases it into your bloodstream. The VLDL particles carry triglycerides, another type of fat, to your tissues. VLDL is similar to LDL cholesterol, but LDL carries cholesterol to your tissues instead of triglycerides.
  3. IgG-to-albumin is a comparison of the levels of IgG to the levels of albumin in the cerebrospinal fluid (CSF). It is used to aid in the diagnosis of multiple sclerosis (MS) The IgG-to-Albumin Ratio CSF Test compares the levels of IgG to the levels of albumin (a common carrier protein) in the cerebrospinal fluid. This may be then compared to the IgG-to-albumin ratio in blood serum. A high value (greater than 0.25) for the IgG-to-Albumin Ratio CSF Test may indicate:  Multiple sclerosis Cerebral or cerebellar atrophy Amyotrophic sclerosis Brain tumor (http://www.dovemed.com/common-procedures/procedures-laboratory/igg-albumin-ratio-csf-test/) IgG index = [IgG (CSF) / IgG (serum)] / [Albumin (CSF) /Albumin (serum)] (https://labtestsonline.org/understanding/conditions/multiplesclerosis/start/2) Prealbumin is a protein that is made in the liver and released in the blood. It helps carry certain hormones that regulate the way the body uses energy and other substances through the blood. When prealbumin levels are lower than normal, it may be a sign of a poor diet (malnutrition). Beta-2 microglobulin, a protein on the cell surface of myeloma and other cells; increased levels may indicate a poorerprognosis; this test may be used to help stage the disease. Hemoglobin A1c test may be used to screen for and diagnose diabetes and prediabetes in adults. Hemoglobin A1c, also glycated hemoglobin or A1c, is formed in the blood when glucose attaches to hemoglobin. The higher the level of glucose in the blood, the more glycated hemoglobin is formed. The test for HbA1c shows how well your diabetes has been controlled over the last 2-3 months. Even though you may have some very high or very low blood glucose values, HbA1c will give you a picture of the average amount of glucose in your blood over that time period. Urinary α1- microglobulin levels were found to be elevated in both type 1 and type 2 diabetic subjects. In type 2 diabetic subjects, α1-microglobulin excretion was directly correlated with albuminuria and HbA1c levels. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083882/)
  4. Amylases are a group of hydrolases that degrade complex carbohydrates into fragments. Amylase is produced primarily by the exocrine pancreas where the enzyme is synthesized by the acinar cells and then secreted into the intestinal tract by way of the pancreatic duct system. Amylases also are produced by the salivary glands, small intestine mucosa, ovaries, placenta, liver, and fallopian tubes. Pancreatic and salivary isoenzymes are found in serum. Amylase is an enzyme, or special protein, produced by your pancreas and salivary glands, Creatine Kinase (CK) To detect and monitor muscle damage; to help diagnose conditions associated with muscle damage; for heart attack detection, this test has been largely replaced by troponin T and I– markers more specific to cardiac tissue; however, it may sometimes be used to help detect a second or subsequent heart attack. Serum glutamic oxaloacetic transaminase (GOT) and serum glutamic pyruvic transaminase (GPT).
  5. 25-(OH)2 Vitamin D3: The biologically active form of vitamin D is 1,25-dihydroxyvitamin D (1,25(OH)2 D). Measuring serum levels of 1,25(OH)2 D should be considered upon suspicion of deficiency or excess of 1,25(OH)2 D. Calcitriol (INN), also called 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3, is the hormonally active metabolite of vitamin D with three hydroxyl groups (abbreviated 1,25-(OH)2D3 or simply 1,25(OH)2D), It was first identified by Michael F. Holick in work published in 1971. Calcitriol increases the level of calcium(Ca2+) in the blood by increasing the uptake of calcium from the gut into the blood, and possibly increasing the release of calcium into the blood from bone. Intact PTH is the most frequently ordered parathyroid hormone test. It is used to help diagnose the cause of a low or high calcium level and to help distinguish between parathyroid-related and non-parathyroid-related causes. It may also be used to monitor the effectiveness of treatment when an individual has a parathyroid-related condition. PTH is routinely monitored for people with chronic kidney disease or who are on dialysis. N-MID Osteocalcin serum: to monitoring and assessing effectiveness of antiresorptive therapy in patients treated for osteopenia, osteoporosis, Paget's disease, or other disorders in which osteocalcin levels are elevated. Osteocalcin is a protein found in bone and teeth. It is secreted by bone-building cells, called osteoblasts, and is deposited inside the bone matrix. Serum osteocalcin represents the fraction of the total produced that has not been placed inside the bone matrix. Osteocalcin is often used as a biochemical marker, or biomarker, for the bone formation process. It has been routinely observed that higher serum osteocalcin levels are relatively well correlated with bone diseases characterized by increased bone turnover, especially osteoporosis.
  6. ACTH levels in the blood are measured to help detect, diagnose, and monitor conditions associated with excessive or deficient cortisol in the body. ... Cushing disease: excess cortisol that is due to an ACTH-producing tumor in the pituitary gland (usually a benign tumor)
  7. CK-MB : This test measures the amount of an isoenzyme of creatine kinase (CK) in your blood. It is called CK-MB. Your body makes 3 forms of CK, including CK-MB. CK is found in the heart, muscles, and other organs. These include the small intestine, brain, and uterus. If you have a heart attack, injured heart muscle cells release CK-MB into your blood. Because many tissues contain CK, high levels of CK can be a sign of a variety of problems. Higher CK-MB may point more directly to heart damage. CPK-MB testMedical diagnostics Kinetics of cardiac markers in myocardial infarction with or without reperfusion treatment. The CPK-MB test is a cardiac marker used to assist diagnoses of an acute myocardial infarction. It measures the blood level of CK-MB (creatine kinase-muscle/brain), the bound combination of two variants (isoenzymes CKM and CKB) of the enzyme phosphocreatine kinase.
  8. Atherogenic index of plasma (AIP) is a logarithmically transformed ratio of molar concentrations of triglycerides to HDL-cholesterol. The strong correlation of AIP with lipoprotein particle size may explain its high predictive value. Lactate dehydrogenase (LDH) is an enzyme required during the process of turning sugar into energy for your cells. LDH is present in many kinds of organs and tissues throughout the body, including the liver, heart, pancreas, kidneys, skeletal muscles, lymph tissue, and blood cells. When illness or injury damages your cells, LDH may be released into the bloodstream, causing the level of LDH in your blood to rise. High levels of LDH in the blood point to acute or chronic cell damage, but additional tests are necessary to discover its cause. Abnormally low LDH levels only rarely occur and usually aren’t considered harmful. To measure whether you have tissue damage and, if so, how much To monitor severe infections or conditions like hemolytic or megaloblastic anemias, kidney disease, and liver disease To help evaluate certain cancers or your cancer treatment Depending on your condition, you may have LDH tests on a regular basis. You might have an LDH test of body fluids to: Find the cause of fluid buildup. It could be due to many things, like injury and inflammation. (It could also be brought on by an imbalance in the pressure within blood vessels and the amount of protein in your blood.) Help determine if you have bacterial or viral meningitis.